Thursday, January 05, 2017

2017 is certainly shaping up to be a big year for nanopore news. I touched on Oxford Nanopore's very full plate in my speculation about sequencing platforms and we already know of two different legal actions which will be progressing, PacBio vs. Oxford Nanopore and University of California vs. Genia. James Hadfield's take on possible Illumina announcements at the J.P. Morgan Conference includes an Illumina nanopore device. That's speculation; today we had a pair of tweets from Two Pore Guys previewing their sensing device and that they will be talking more at J.P. Morgan (all videos from 2PG).

Two Pore Guys (2PG from here out) has been developing a platform in which, per their name, analytes are sent through two solid state nanopores in series. Their argument, found in their collection of videos, is that a high degree of molecule translocation speed can be achieved with this scheme. The pores are quite long, around 60 nucleotides in length, so this scheme is not trying to sequence DNA (though their video suggests other technologies could be layered in to perform sequencing). Rather, by attaching capture reagents to DNA (or in the new video, some unspecified DNA-like molecule) the presence of captured molecules or particles can be detected. TPG envisions a handheld device akin to a glucose sensor which would execute tests in a disposable microfluidic chip.

The new 2PG video largely reiterates the concept of the old video, but now shows a test being run to detect anti-HIV antibodies. First a negative control is run; a cheek swab is collected and dunked in a liquid, which is then applied with a simple dropper onto the device. No signal, since no HIV. If the sample is spiked with a control anti-HIV antibody from a commercial chip, then signal is seen rapidly.

The appeal of t2PG's device as shown is obvious. No sample prep and no precision pipetting. Furthermore, TPG suggests that any existing capture reagent can be easily attached to their strands, potentially enabling any existing immunoassay or other binding assay to be converted to this format. They also promise that in the future the entire assay would be lyophilized on the chip; just add sample and go. Plus a wide range of biological sample types are listed as having been tested in this format, including just about anything a doctor might ask you to provide.

That's a great vision, but clearly this would need to be vetted on a large scale. Even if Theranos hadn't blown up into a huge, ugly mess nobody should just assume that a flashy new assay tech will simply work.

The new 2PG video doesn't discuss multiplexing analytes, but an older one does suggest this is possible by tagging the capture strands with labels. That video suggests that not only could a large number of analytes be multiplexed, but metadata on the test could also be included within the assay.

It is easy to dream of attaching oligonucleotide capture reagents to the sensors to enable facile RNA profiling of samples. The ability to rapidly profile many capture reagents in parallel within the same sample would also enable the optimization and selection of such reagents. The quality of antibodies is often poorly understood, and that is in part because it is troublesome to characterize them. 2PG's approach could possibly compete or complement assays for determining affinity such as Surface Plasmon Resonance (SPR); potentially the change in the signal over the running of the assay could give at least crude information on binding kinetics (i.e. as molecules associated the number of strands bearing analytes would trend in a manner suggesting the kinetics).

Someone at Illumina once told me, "You'd be crazy to think that Illumina wasn't working on a nanopore device."

2PG has a cool looking device. I think people underappreciate the applications with this technology. It's a quantitative counting device that can go from sample to answer in seconds to minutes (bye bye ddPCR). Some applications will clearly require an upstream DNA extraction. You can't do liquid biopsy without sampling at least 10mL of blood, but the speed and ease of use of this device is revolutionary. There will be a lot of applications where this is immediately beneficial. Can you imagine converting any ELISA into a cheek swab test that takes seconds? That will be a boon for infectious disease research and in field diagnostic testing, just to name one application.

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About Me

Dr. Robison spent 10 years at Millennium Pharmaceuticals working with various genomics & proteomics technologies & working on multiple teams attempting to apply these throughout the drug discovery process. He spent 2 years at Codon Devices working on a variety of protein & metabolic engineering projects as well as monitoring a high-throughput gene synthesis facility. After a brief bit of consulting, he rejoined the cancer drug discovery field at Infinity Pharmaceuticals in May 2009. In September 2011 he joined Warp Drive Bio, a startup applying genomics to natural product drug discovery. Other recurring characters in this blog are his loyal Shih Tzu Amanda and his teenaged son alias TNG (The Next Generation).
Dr. Robison can be reached via his Gmail account, keith.e.robison@gmail.com
You can also follow him on Twitter as @OmicsOmicsBlog.